In depth

Mar 17, 2006

Nanoparticle size affects uptake by cells

Researchers at the University of Toronto, Canada, have found that the rate of uptake of gold nanoparticles by mammal cells depends on the particle size and shape. The study could have implications for the design of nanostructures for biomedical uses such as drug delivery and imaging.

"There have been numerous studies using nanoparticles for applications in cell biology, e.g. fluorescence labelling, drug delivery," Warren Chan of the University of Toronto told nanotechweb.org. "No-one has really looked at how the nanostructures' size and morphology affect how they go into the cell. Figuring this relationship can help researchers improve detection sensitivity, drug delivery efficiency, etc. In addition, this can help us assess the toxicity of an engineered nanostructure."

Chan and colleagues studied gold nanoparticles that were between 14 and 100 nm and had both spherical and rod-shaped morphologies. They incubated the nanoparticles with HeLa cells for six hours in a growth medium solution containing 10% serum. Using inductively coupled plasma atomic emission spectroscopy then revealed the concentration of gold inside the cells.

The HeLa cells took up most nanoparticles when the particles were 50 nm. The nanoparticles entered the cells and were trapped inside vesicles in the cytoplasm but did not enter the cell nucleus. The maximum number of 50 nm nanoparticles entering a cell was 6160, while 15 nm and 74 nm particles lagged behind at 3000 and 2988 respectively.

Chan and colleagues believe that the mechanism for the process was receptor-mediated endocytosis. They reckon that the gold nanoparticles adsorb serum proteins nonspecifically onto their surface. The proteins then facilitate entry into the cell via receptors on the cell membrane.

Shape also played an important role. The cells took up fewer rod-shaped nanoparticles than spherical nanoparticles. For example, cells ingested 500 and 375% more 74 and 14 nm spherical nanoparticles than 74 x 14 nm rod-shaped particles. The team believes this may be due to the difference in curvature affecting the contact area with the cell membrane receptors, or to the presence of cetyl trimethylammonium bromide surfactant molecules on the rod-shaped nanoparticle surfaces from the synthesis process.

Citrate-stabilized gold nanoparticles were taken up by the cells to a greater extent than transferrin-coated nanoparticles. The researchers believe this was because the surface of the citrate-stabilized nanoparticles contained a variety of serum proteins on its surface. This is likely to have enabled entry into the cells via multiple receptors rather than the two receptors that the protein transferrin corresponds to.

According to the researchers, these results should enable them to tune the delivery of proteins, drugs and oligonucleotides to cells by altering the size and shape of the nanoparticles to which they are attached. "The nonspecific adsorption of serum proteins may dictate the cellular fate, uptake, metabolism and clearance of nanoparticles," they write in their paper.